Annemarie Wasley

The Prevalence of Hepatitis C Virus Infection in the United States, 1999 through 2002

Context The Third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988 and 1994, indicated that 1.8% of people in the United States had been infected with hepatitis C virus (HCV), 70% of whom had chronic infection. Most anti-HCVpositive individuals were between 30 and 49 years of age. Contribution Data from the recent NHANES (19992002) show little change in anti-HCV prevalence, but peak prevalence has shifted to individuals between 40 and 49 years of age. More than 85% of HCV RNApositive individuals may be identified through targeted testing of 18% of adults between 20 and 59 years of age: persons with abnormal serum alanine aminotransferase levels, those who have used injection drugs, and those who received blood transfusions before 1992. Cautions Incarcerated and homeless people were not included in the survey. Implications Despite a decrease in new HCV infections, aging of chronically infected individuals may presage an imminent increase in complications. The Editors A decade ago, the Third National Health and Nutrition Examination Survey (NHANES III, 19881994) showed hepatitis C virus (HCV) to be the most common chronic bloodborne infection in the United States (1). An estimated 3.9 million people (1.8% of the population) tested positive for antibody to HCV (anti-HCV), and 2.7 million had chronic infection. Most (65%) anti-HCVpositive persons were 30 to 49 years of age and had been infected for fewer than 20 years. The genetic diversity of HCV circulating in the United States (2) and the pattern of age-specific prevalence (3, 4) both suggest that the incidence of infection increased substantially in the 1960s and 1970s and peaked in the 1980s. Identification of HCV-positive persons for appropriate counseling and management is the major focus of a national prevention program, and routine testing is recommended for persons most likely to have HCV infection (5). To determine the characteristics of HCV-infected persons in the general United States population today and to monitor trends in prevalence, we analyzed data on HCV infection from the most recent NHANES. Methods The National Center for Health Statistics has conducted NHANES periodically to compile nationally representative statistics on the health of the U.S. population (6). The most recent series was begun in 1999 and is designed to run continuously; data are released every 2 years. Our analysis includes data collected from 1999 through 2002. Participants were chosen according to a stratified, multistage algorithm to produce a representative sample of the civilian, noninstitutionalized population of all 50 states and the District of Columbia. Extensive efforts were made to ensure high participation rates, and all respondents were reimbursed for time and travel expenses (6). Initially, a questionnaire covering only nonsensitive topics was used to interview participants in person at home. Information on potentially sensitive subjects, such as sexual practices and illicit drug use, was obtained later at a mobile examination center by means of computer-assisted interviewing technology. The ethnicity of each participant was categorized as non-Hispanic white, non-Hispanic black, and Mexican American. Persons not fitting these categories were classified as other and were included in the total population. Blood samples were obtained at the mobile examination center (7). Only participants who were 6 years of age or older were eligible for HCV testing because of low sample volume in younger children. Laboratory Methods Serum specimens were sent to the Centers for Disease Control and Prevention, where they were tested for anti-HCV by using Ortho HCV enzyme-linked immunosorbent assay (ELISA), version 3.0 (Ortho-Clinical Diagnostics, Raritan, New Jersey). Supplemental recombinant immunoblot assays (RIBA) (Chiron RIBA HCV Strip Immunoblot Assay, version 3.0, Chiron Corp., Emeryville, California) were performed on all specimens that were repeatedly reactive by ELISA testing. For those specimens classified as positive or indeterminate by RIBA, separate, archived aliquots stored at 70C and suitable for nucleic acid amplification testing were submitted for quantitative HCV RNA testing using Cobas Amplicor HCV Monitor Test, version 2.0 (Roche Molecular Diagnostics, Pleasanton, California). If that result was below the level of detection, a qualitative assay (Amplicor HCV Test, version 2.0, Roche Molecular Diagnostics) was performed. Samples found to be reactive by enzyme immunoassay and confirmed by RIBA or Amplicor were considered to be anti-HCVpositive. Alanine aminotransferase (ALT) levels (reference range, 0 to 39 U/L) were measured in specimens that had been stored and shipped under appropriate refrigeration conditions (4C to 8C). Statistical Analysis All statistical analyses were performed with SUDAAN software (RTI International, Research Triangle Park, North Carolina) according to National Center for Health Statistics guidelines. We used appropriate study design variables and published weights that were further adjusted to compensate for missing anti-HCV values (8). These weights accounted for oversampling of certain demographic groups (6) and for nonparticipation such that the sum of the weights for persons with anti-HCV results equaled the U.S. civilian, noninstitutionalized population 6 years of age and older. To estimate the number of HCV RNApositive persons, these weights were further adjusted to compensate for the RIBA-positive and RIBA-indeterminate specimens that were unavailable for RNA testing because of inadequate specimen volumes. Proportions from univariable analyses were compared by using chi-square tests (as implemented in SUDAAN). The P values presented were not corrected for multiple comparisons; P values less than 0.05 were considered statistically significant. Two logistic regression models were used for multivariable analysis; 1 model was used for persons 20 to 59 years of age whose drug use and sexual practices data were available, and the other model was used for persons 60 years of age or older. Two variables, history of blood transfusion (both models) and injection drug use (persons 20 to 59 years of age), were forced into the models on the basis of substantial published data that has established them as risk factors for HCV infection. We sought the most parsimonious model by using these and all other variables that were significant at a P value less than 0.20 on univariable analysis. With the resulting model, we then examined the effect of adding other variables of interest, including those variables that had been excluded at earlier steps in the modeling process. In the final models, all first-order interactions were examined for statistical significance, epidemiologic plausibility, and the impact of their inclusion on the other model parameters. Role of the Funding Source No external funding was received for this study. Results Of 21509 participants 6 years of age or older, 17548 were interviewed and 15079 gave a blood sample suitable for anti-HCV testing (final response rate for testing, 70.1%). Among those who completed home interviews, participation rates did not differ significantly between those with and without risk factors for HCV infection. The weighted prevalence of anti-HCV in the United States was 1.6% (95% CI, 1.3% to 1.9%), corresponding to 4.1 million (CI, 3.4 million to 4.9 million) anti-HCVpositive persons (Table 1). Of anti-HCVpositive participants, 78.8% had specimens suitable for HCV RNA testing; 79.7% (CI, 70.4% to 86.6%) of these tested positive for HCV RNA. After we accounted for untested specimens, the nationwide prevalence of HCV RNA among all participants was 1.3% (CI, 1.0% to 1.5%), equating to 3.2 million (CI, 2.7 million to 3.9 million) HCV RNApositive persons. Table 1. Prevalence of Antibody to Hepatitis C Virus by Demographic Characteristics and Potential Risk Factors Demographic Characteristics Associated with HCV Infection Anti-HCV prevalence was significantly higher in men than in women (Table 1). Prevalence was also higher in non-Hispanic black participants than in either of the other 2 ethnic groups. Among persons younger than 50 years of age, prevalence of anti-HCV increased with age from 1.0% in those 20 to 29 years of age to a peak of 4.3% in those 40 to 49 years of age (Figure 1). Among older persons, anti-HCV prevalence decreased to 1.6% in persons 50 to 59 years of age and to 0.9% in persons 60 years of age and older. Prevalence was higher in men than in women in most age groups (Figure 1). The higher overall prevalence among non-Hispanic black persons compared with non-Hispanic white persons was almost entirely attributable to differences among older participants. Among participants 40 to 49 years of age, 9.4% of non-Hispanic black persons had positive results for anti-HCV compared with 3.8% of non-Hispanic white persons (P< 0.001); of participants 50 years of age or older, 3.3% of non-Hispanic black persons had positive results compared with 0.9% of non-Hispanic white persons (P= 0.002). The demographic group with the highest prevalence was non-Hispanic black men between 40 and 49 years of age (13.6% [CI, 10.0% to 18.2%]). Prevalence was not significantly different between non-Hispanic black and non-Hispanic white persons who were younger than 40 years of age (1.2% vs. 1.1%; P= 0.73). Participants who were born in the United States had a higher prevalence of anti-HCV than those who were not, and prevalence increased with decreasing family income and level of education (Table 1). Among men, prevalence did not vary according to service in the military (Table 1). The sample of women who had served in the military was too small to analyze. Figure 1. Prevalence of antibodies to hepatitis C virus ( HCV ) by ethnicity, age, and sex. The overall prevalence of anti-HCV in the current survey was similar to that observed in NHANES III, but the peak in age-specific prevale

Epidemiology of Hepatitis E Virus in the United States: Results from the Third National Health and Nutrition Examination Survey, 1988–1994

BACKGROUND Hepatitis E virus (HEV) is prevalent and causes disease worldwide, but its epidemiological profile is only partially understood. METHODS We used an enzyme immunoassay to measure anti-HEV immunoglobulin G antibodies in 18,695 serum samples collected in the Third National Health and Nutrition Examination Survey. We calculated estimates of HEV seroprevalence and examined associations with putative risk factors. RESULTS The seroprevalence of HEV in the civilian noninstitutionalized United States (US) population during the period from 1988 through 1994 was 21.0% (95% confidence interval [CI], 19.0%-22.9%). Among US-born individuals, males, non-Hispanic whites, and individuals residing in the Midwest and/or in metropolitan areas had the highest seroprevalence estimates. Having a pet in the home (odds ratio [OR], 1.19 [95% CI, 1.01-1.40]) and consuming liver or other organ meats more than once per month (OR, 1.38 [95% CI, 1.01-1.88]) were significantly associated with increased odds of HEV seropositivity. CONCLUSIONS Exposure to HEV is common in the US population, although hepatitis E is rarely reported. Having pets and consuming organ meats may play a role in HEV transmission in the United States, but other mechanisms of transmission may also exist. HEV may be considered a possible etiologic agent of acute and chronic hepatitis in US patients reporting no travel history.

The Increasing Burden of Imported Chronic Hepatitis B — United States, 1974–2008

Background Without intervention, up to 25% of individuals chronically infected with hepatitis B virus (HBV) die of late complications, including cirrhosis and liver cancer. The United States, which in 1991 implemented a strategy to eliminate HBV transmission through universal immunization, is a country of low prevalence. Approximately 3,000–5,000 U.S.-acquired cases of chronic hepatitis B have occurred annually since 2001. Many more chronically infected persons migrate to the United States yearly from countries of higher prevalence. Although early identification of chronic HBV infection can reduce the likelihood of transmission and late complications, immigrants are not routinely screened for HBV infection during or after immigration. Methods To estimate the number of imported cases of chronic hepatitis B, we multiplied country-specific prevalence estimates by the yearly number of immigrants from each country during 1974–2008. Results During 1974–2008, 27.9 million immigrants entered the U.S. Sixty-three percent were born in countries of intermediate or high chronic hepatitis B prevalence (range 2%–31%). On average, an estimated 53,800 chronic hepatitis B cases were imported to the U.S. yearly from 2004 through 2008. The Philippines, China, and Vietnam contributed the most imported cases (13.4%, 12.5%, and 11.0%, respectively). Imported cases increased from an estimated low of 105,750 during the period 1974–1977 to a high of 268,800 in 2004–2008. Conclusions Imported chronic hepatitis B cases account for approximately 95% of new U.S. cases. Earlier case identification and management of infected immigrants would strengthen the U.S. strategy to eliminate HBV transmission, and could delay disease progression and prevent some deaths among new Americans.

SARS Surveillance during Emergency Public Health Response, United States, March-July 2003

In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.

Seroprevalence of hepatitis A virus antibodies in the U.S.: results from the National Health and Nutrition Examination Survey.

Objectives. We described seroprevalence of antibody to hepatitis A virus (anti-HAV) in the United States during 1999–2006 and compared it with seroprevalence before the availability of vaccine. Methods. We analyzed data from the 1988–1994 and 1999–2006 National Health and Nutrition Examination Survey (NHANES) to obtain estimates of anti-HAV seroprevalence for the U.S. household population. We grouped region of residence based on the 1999 Advisory Committee on Immunization Practices recommendations into 17 states with any recommendation (vaccinating) and 33 states without any recommendation (non-vaccinating). Results. During 1999–2006, the overall seroprevalence of anti-HAV was 34.9% (95% confidence interval [CI] 33.1, 36.7). During 1999–2006, U.S.-born children living in vaccinating states (33.8%, 95% CI 26.2, 42.2) had a higher seroprevalence than children in non-vaccinating states (11.0%, 95% CI 9.4, 12.8; p<0.001). Seroprevalence among children increased from 8.0% (95% CI 6.3, 10.1) during 1988–1994 to 20.2% (95% CI 16.0, 24.8) during 1999–2006 (p<0.001). For U.S.-born children aged 6–19 years, the strongest factor associated with seroprevalence was residence in vaccinating states. Among U.S.-born adults aged >19 years, the overall age-adjusted seroprevalence of anti-HAV was 29.9% (95% CI 28.3, 31.5) during 1999–2006, which was not significantly different from the seroprevalence during 1988–1994 (32.2%, 95% CI 30.1, 34.4). Conclusions. Increases in seroprevalence among children in vaccinating states suggest a positive effect of the 1999 vaccination recommendations.

Correction: The Increasing Burden of Imported Chronic Hepatitis B — United States, 1974–2008

[This corrects the article DOI: 10.1371/journal.pone.0027717.].